Medulloblastoma is the most common paediatric malignant brain tumour, accounting for around 20% of all childhood brain cancer cases. Medulloblastoma tumours are highly aggressive and standard treatment options such as radiotherapy, chemotherapy, and surgery carry potentially severe side-effects. Medulloblastoma presents a unique model to study the epigenome as the mutational burden of tumours is exceptionally low compared to other tumour types, both brain and other sites of origin. Therefore, the epigenome is thought to play a major role in medulloblastoma tumourigenesis. Four molecular subgroups of medulloblastoma can be categorised based on transcriptional and epigenetic profiles which are Wingless (WNT), Sonic hedgehog (SHH), Group 3 and Group 4.
To create a comprehensive in vitro model of medulloblastoma, we sought to profile various layers of epigenetic regulation in medulloblastoma cell lines from the SHH-group (ONS-76 and Daoy) and Group 3 (D341). We initially examined the underlying mutational status of key epigenetic regulator genes using whole genome sequencing, coupled with baseline gene and protein expression profiling. Targets that were of particular interest included SWI/SNF chromatin remodeler ATPases, 3D chromatin looping proteins, DNA methyltransferases and also BRCA1, which is known to interact with key epigenetic regulators. Genome wide-binding patterns were assessed using the CUT&RUN assay for BRG1, BRM and CTCF. This data will be combined with histone modification and DNA methylation signatures to further elucidate the epigenetic programs controlling medulloblastoma cell biology. Moreover, this research provides an extensive resource for in vitro studies of medulloblastoma by determining the underlying epigenetic profiles of commonly used cell lines.